Mfge8 Promotes Obesity by Mediating the Uptake of Dietary Fats and Serum Fatty Acids

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2014 Jan 21

PMID 24441829

Citations 54

Authors

Amin Khalifeh-Soltani

William McKleroy

Stephen Sakuma

Yuk Yin Cheung

Kevin Tharp

Yifu Qiu

Scott M Turner

Ajay Chawla

Andreas Stahl

Kamran Atabai

Affiliations

Soon will be listed here.

Abstract

Fatty acids are integral mediators of energy storage, membrane formation and cell signaling. The pathways that orchestrate uptake of fatty acids remain incompletely understood. Expression of the integrin ligand Mfge8 is increased in human obesity and in mice on a high-fat diet, but its role in obesity is unknown. We show here that Mfge8 promotes the absorption of dietary triglycerides and the cellular uptake of fatty acid and that Mfge8-deficient (Mfge8(-/-)) mice are protected from diet-induced obesity, steatohepatitis and insulin resistance. Mechanistically, we found that Mfge8 coordinates fatty acid uptake through αvβ3 integrin- and αvβ5 integrin-dependent phosphorylation of Akt by phosphatidylinositide-3 kinase and mTOR complex 2, leading to translocation of Cd36 and Fatp1 from cytoplasmic vesicles to the cell surface. Collectively, our results imply a role for Mfge8 in regulating the absorption and storage of dietary fats, as well as in the development of obesity and its complications.

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